The Open Neurology Journal




ISSN: 1874-205X ― Volume 14, 2020

Study of a Functional Polymorphism in the PER3 Gene and Diurnal Preference in a Colombian Sample



Claudia S Perea 1, Carmen L Niño 2, Sandra López-León 3, Rafael Gutiérrez 4, Diego Ojeda 1, Humberto Arboleda 5, Andrés Camargo 2, Ana Adan 6, Diego A Forero *
1 Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño. Bogotá, Colombia
2 School of Nursing, Universidad de Ciencias Aplicadas y Ambientales UDCA. Bogotá, Colombia
3 Global Clinical Epidemiology, Novartis Pharmaceuticals Corporation, New Jersey, USA
4 Complex Systems Group, Research Center for Basic and Applied Sciences, Universidad Antonio Nariño, Bogotá, Colombia
5 Neurosciences Research Group, School of Medicine, Universidad Nacional de Colombia. Bogotá, Colombia
6 Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain

Abstract

Polymorphisms in human clock genes have been evaluated as potential factors influencing circadian phenotypes in several populations. There are conflicting results for the association of a VNTR in the PER3 gene and diurnal preference in different studies. The objective of this study was to investigate the association between diurnal preference and daytime somnolence with the PER3 VNTR polymorphism (rs57875989) in healthy subjects from Colombia, a Latin American population.A total of 294 undergraduate university students from Bogotá, Colombia participated in this study. Two validated self-report questionnaires, the Composite Scale of Morningness (CSM) and the Epworth Sleep Scale (ESS) were used to assess diurnal preference and daytime somnolence, respectively. Individuals were genotyped for the PER3 VNTR using conventional PCR. Statistical comparisons were carried out with PLINK and SNPStats programs.

The PER3 VNTR polymorphism was not associated with either diurnal preference or daytime somnolence in this population. No significant differences in mean scores for those scales were found between PER3 VNTR genotypes. In addition, there were no differences in allelic or genotypic frequencies between chronotype categories. This is consistent with several negative findings in other populations, indicating that the proposed influence of this polymorphism in diurnal preference, and related endophenotypes of neuropsychiatric importance, needs further clarification. This is the first report of molecular genetics of human circadian phenotypes in a Spanish-speaking population.

Keywords: Chronobiology, endophenotypes, genetics, Latin America, molecular genetics, neuropsychiatric neurogenetics, sleep.


Article Information


Identifiers and Pagination:

Year: 2014
Volume: 8
First Page: 7
Last Page: 10
Publisher Id: TONEUJ-8-7
DOI: 10.2174/1874205X01408010007

Article History:

Received Date: 10/1/2014
Revision Received Date: 24/3/2014
Acceptance Date: 25/3/2014
Electronic publication date: 18 /4/2014
Collection year: 2014

© Perea et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the Laboratory of Neuro Psychiatric Genetics, Universidad Antonio Nariño. Bogotá, Colombia; Tel: +57 313 2610427; Fax: + 57 1 2856480; E-mail: diego.forero@uan.edu.co





INTRODUCTION

Diurnal preference is a well-known circadian phenotype based on the favorite timing of daily activities [1Adan A, Archer SN, Hidalgo MP, Di Milia L, Natale V, Randler C. Circadian typology: a comprehensive review Chronobiol Int 2012; 29: 1153-75.]. There is a high variability for this preference among the general population, which has been the basis for a further categorization of this characteristic in a phenotype known as chronotype [1Adan A, Archer SN, Hidalgo MP, Di Milia L, Natale V, Randler C. Circadian typology: a comprehensive review Chronobiol Int 2012; 29: 1153-75.]. Several polymorphisms in classical “clock” genes, such as Period homolog 3 (PER3) or Clock homologue (CLOCK), have been studied as possible genetic correlates of chronotypes and other circadian phenotypes in healthy humans [2Archer SN, Robilliard DL, Skene DJ, et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference Sleep 2003; 26: 413-5.-7Nievergelt CM, Kripke DF, Barrett TB, et al. Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 234-41.].

A variable-number tandem repeat (VNTR) polymorphism (rs57875989) in the PER3 gene (located on chromosome 1p36.23), consisting of two alleles of four or five tandem 54 bp repeats (coding for a region of 18 amino acids in exon 18), has been evaluated as a potential genetic factor for chronotypes and other circadian phenotypes [2Archer SN, Robilliard DL, Skene DJ, et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference Sleep 2003; 26: 413-5., 5Ebisawa T, Uchiyama M, Kajimura N, et al. Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome EMBO Rep 2001; 2: 342-6.]. However, previous findings in several populations have been inconsistent [2Archer SN, Robilliard DL, Skene DJ, et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference Sleep 2003; 26: 413-5., 6Pereira DS, Tufik S, Louzada FM, et al. Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it? Sleep 2005; 28: 29-32., 7Nievergelt CM, Kripke DF, Barrett TB, et al. Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 234-41.] and it has been hypothesized that intrinsic factors of the populations, such as latitude and genetic background, may have an effect on these associations [1Adan A, Archer SN, Hidalgo MP, Di Milia L, Natale V, Randler C. Circadian typology: a comprehensive review Chronobiol Int 2012; 29: 1153-75., 6Pereira DS, Tufik S, Louzada FM, et al. Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it? Sleep 2005; 28: 29-32.].

The aim of this study was to perform a replication of the previous studies of the association of VNTR polymorphism in PER3 and diurnal preference in a sample of healthy young subjects from Bogotá, Colombia, a South American popu-lation.

MATERIALS AND METHODOLOGY

Subjects

A total of 294 healthy undergraduate students (66.6% female, mean age [SD] was 20.5 [2.7] years, range: 18-30 years) of two private universities in the capital city of Colombia (Bogotá) (04º 38′ N, 74°05′ W) participated voluntarily in the study. Additional 24 samples (7.5% of the total sample) were excluded from the final analysis due to incomplete phenotypic or genetic data. The population living in Bogotá is composed of a European genetic background with some historical admixture with Amerindians [8Forero DA, Arboleda G, Yunis JJ, Pardo R, Arboleda H. Association study of polymorphisms in LRP1. tau and 5-HTT genes and Alzheimer's disease in a sample of Colombian patients J Neural Transm 2006; 113: 1253-62.]. Subjects with self-report of neuropsychiatric diseases, including sleep disor-ders, were excluded. This study was approved by the Institutional Ethics Committee of each participant institution and all subjects provided written informed consent [8Forero DA, Arboleda G, Yunis JJ, Pardo R, Arboleda H. Association study of polymorphisms in LRP1. tau and 5-HTT genes and Alzheimer's disease in a sample of Colombian patients J Neural Transm 2006; 113: 1253-62.].

Phenotypic Evaluations

To measure and characterize the circadian phenotypes each participant filled out two self-report scales, previously validated and widely used in other populations [9Caci H, Adan A, Bohle P, Natale V, Pornpitakpan C, Tilley A. Transcultural properties of the composite scale of morningness: the relevance of the "morning affect" factor Chronobiol Int 2005; 22: 523-40.]: Composite Scale of Morningness (CSM) and Epworth Sleep Scale (ESS) [10Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale Sleep 1991; 14: 540-., 11Smith CS, Folkard S, Schmieder RA, et al. Investigation of morning–evening orientation in six countries using the preferences scale Pers Individ Dif 2002; 32: 949-68.].

Composite Scale of Morningness (CSM)

The CSM scale consists of 13 questions regarding the preferred times for mental and physical activity as well as the subjective alertness of the individuals. The total score of the CSM questionnaire is obtained by adding the individual scores of all the items, and it ranges from 13 (extreme eveningness) to 55 (extreme morningness). CSM has shown a strong correlation with other commonly used scales, such as the Horne-Östberg Morningness-Eveningness Question-naire (given the fact that some of the scales consist of similar items), and with objective measures derived from actigraphy [12Thun E, Bjorvatn B, Osland T, et al. An actigraphic validation study of seven morningness-eveningness inventories Eur Psychol 2012; 17: 222-30.]. In this study, we have used the validated version in Spanish of the CSM [13Adan A, Caci H, Prat G. Reliability of the Spanish version of the Composite Scale of Morningness Eur Psychiatry 2005; 20: 503-9.], that has been previously used in a Colombian sample [11Smith CS, Folkard S, Schmieder RA, et al. Investigation of morning–evening orientation in six countries using the preferences scale Pers Individ Dif 2002; 32: 949-68.]. The internal consistency of this scale (Cronbach's alpha) for the present sample was 0.722.

Epworth Sleep Scale (ESS)

The ESS is a widely validated tool to quantify the general level of daytime sleepiness in general population) [10Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale Sleep 1991; 14: 540-., 11Smith CS, Folkard S, Schmieder RA, et al. Investigation of morning–evening orientation in six countries using the preferences scale Pers Individ Dif 2002; 32: 949-68.]. It is a self-administrated questionnaire composed by eight situations of daily life that subjects have to range from 0 to 3 on their propensity to fall asleep. It ranges from 0 to 24, with higher scores related to more sleepiness. This scale has been used in different studies of genetics of circadian phenotypes [14Choub A, Mancuso M, Coppede F, et al. Clock T3111C and Per2 C111G SNPs do not influence circadian rhythmicity in healthy Italian population Neurol Sci 2011; 32: 89-93.-16Lazar AS, Slak A, Lo JC, et al. Sleep. diurnal prefernce.health., and psychological well-being a prospective single allelic-variation study Chronobiol Int 2012; 29: 131-46.]. We used the validated version in Spanish of the ESS [11Smith CS, Folkard S, Schmieder RA, et al. Investigation of morning–evening orientation in six countries using the preferences scale Pers Individ Dif 2002; 32: 949-68.], that has also been used before in a Colombian sample [17Chica-Urzola HL, Escobar-Cordoba F, Eslava-Schmalbach J. [Validating the Epworth sleepiness scale] Rev Salud Publica (Bogota) 2007; 9: 558-67.]. The internal consistency (Cronbach’s alpha) in this sample was 0.716.

Additionally all participants completed a self-administered general questionnaire that was used to collect socio-demographic variables (age, gender and personal history of neuropsychiatric disorders) and additional sleep parameters, such as self-report number of Hours of Sleep during Working Days (HSWD) and number of Hours of Sleep during Weekends (HSW).

DNA Extraction and Genotyping

Genomic DNA was isolated from peripheral blood of participants using a standard salting-out method [8Forero DA, Arboleda G, Yunis JJ, Pardo R, Arboleda H. Association study of polymorphisms in LRP1. tau and 5-HTT genes and Alzheimer's disease in a sample of Colombian patients J Neural Transm 2006; 113: 1253-62.]. Genotyping of the PER3 VNTR (rs57875989) was performed using a touchdown PCR with a final annealing temperature of 56ºC, using the primers and conditions previously described [7Nievergelt CM, Kripke DF, Barrett TB, et al. Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 234-41.]. Two primers were used, which amplify fragments of 310 bp and 364 bp for 4 and 5 alleles, respectively. PCR products were separated in a 2% agarose gel at 140V and visualized with ultraviolet light after SYBR Safe (Invitrogen, Carlsbad, CA, USA) staining. A random subsample (10% of subjects) was reanalyzed for the PER3 polymorphism to verify consistency in the genetic results. Additionally, all genotypes were checked by two different researchers in order to confirm and validate the results.

Statistical Analysis

Allele and genotype frequencies and Hardy-Weinberg Equilibrium (HWE) were calculated with the SNPStats software [18Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies Bioinformatics 2006; 22: 1928-9.]. SNPStats was also used for the analysis of the association of PER3 genotypes with quantitative measures of circadian phenotypes (CSM and ESS scores, HSWD and HSW), using a linear regression model, corrected by sex and age. Codominant, dominant, recessive, overdominant, and log-additive models were tested.

In order to compare the extreme groups of diurnal preferences, the 25th and 75th percentiles of the CSM score distribution were used to define the cut off points to classify the individuals in Evening (values ≤36), Neither (values from 37 to 42), or Morning type (values ≥43) [13Adan A, Caci H, Prat G. Reliability of the Spanish version of the Composite Scale of Morningness Eur Psychiatry 2005; 20: 503-9.]. Similarly, the 75th percentile of the ESE distribution was used to determine the cut-off point (14 points) to classify the population in Normal (values ≤14) or High (values ≥15) categories for diurnal somnolence. The 25th and 75th percentiles were used as cut off points in order to have categories with sample sizes that are suitable for carrying out statistical comparisons of genotype and allele frequencies.

PLINK sofeware (Version 1.01) [19Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses Am J Hum Genet 2007; 81: 559-75.] was used to evaluate the association of PER3 polymorphism with categories of morning preference and diurnal somnolence, using a χ2 test (comparisons of genotype and allele frequencies between categories). For the comparison of genotype frequencies, several models were tested (dominant, recessive and genotypic). A nominal value of p<0.05 was considered as statistically significant.

RESULTS

In this study, we found an allele frequency of 0.8 for the 4 allele of the PER3 VNTR, with the most common genotype being the homozygous 4/4 (0.65). The frequencies of the genotypes for this polymorphism were in Hardy–Weinberg equilibrium (p=0.36). In our sample, the scores for the CSM ranged from 24 to 54, with a mean of 39.74 (SE: 0.32) and the ESS had scores from 0 to 21 with a mean of 10.89 (SE: 0.25). In our sample, the scores for the CSM ranged from 24 to 54, with a mean of 39.76 (SE:0.33) and the ESS had scores from 0 to 21 with a mean of 10.93 (SE:0.26).

The linear regression model, corrected by sex and age, showed no differences in scores for the CSM or ESS scales between carriers of the PER3 genotypes (Table 1), under several genotypic models. Self-reported hours of sleep (HSWD and HSW) were not associated with the PER3 VNTR polymorphism in our sample (p= 0.25 and p=0.49).

Table 1

Association of the PER3-VNTR with (A) Scores of the Composite Scale of Morningness (CSM) and its categorization in morning/neutral/evening chronotypes and (B) Scores of the Epworth Sleep Scale (ESS) and its categorization in High/ Low somnolence.








Moreover, the distribution of the genotypes and alleles was not significant between the extreme morning preference and somnolence categories (Table 1), under several genotypic models. Inclusion of additional covariates, such as sex, did not help to identify positive associations (data not shown).

DISCUSSION

This is the first study carried out in the Colombian population regarding the association of a variant in a clock gene (PER3) and circadian phenotypes (diurnal preference and diurnal somnolence). In this study we did not confirm the association between the PER3 VNTR and neither of the phenotypes measured, using different types of analysis and genetic models.

Both positive and negative results have been previously reported for this association. Few studies in Caucasian populations have confirmed this association [2Archer SN, Robilliard DL, Skene DJ, et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference Sleep 2003; 26: 413-5., 6Pereira DS, Tufik S, Louzada FM, et al. Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it? Sleep 2005; 28: 29-32., 16Lazar AS, Slak A, Lo JC, et al. Sleep. diurnal prefernce.health., and psychological well-being a prospective single allelic-variation study Chronobiol Int 2012; 29: 131-46.] while several others have failed to replicate it [3Barclay NL, Eley TC, Mill J, et al. Sleep quality and diurnal preference in a sample of young adults: associations with 5HTTLPR.ER3.and CLOCK 3111. Am J Med Genet B Neuropsychiatr Genet 2011; 156B: 681-90., 20Osland TM, Bjorvatn BR, Steen VM, Pallesen S. Association study of a variable-number tandem repeat polymorphism in the clock gene PERIOD3 and chronotype in Norwegian university students Chronobiol Int 2011; 28: 764-0.]. Colombia is a South American country that lies near to the Equator. These geographic characteristics make it different from the previous populations studied; there are no major seasonal changes through the entire year. It may explain, in addition to differences in genetic background, the lack of association with morning preference that we found here.

This is the first report of circadian phenotypes related to clock genes in a Spanish speaking population and in subjects living in the equatorial region. In addition, it highlights the importance of analyzing South American populations as a complement to the European populations commonly studied, to generate a better understanding of their role in circadian phenotypes [6Pereira DS, Tufik S, Louzada FM, et al. Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it? Sleep 2005; 28: 29-32.]. A meta-analysis on this association should be carried out to have a real quantitative measure of the effect of this polymorphism in different populations. Future analysis of other candidate functional polymorphisms on the PER3 gene and other clock genes could be helpful for the genetic analysis of circadian phenotypes [1Adan A, Archer SN, Hidalgo MP, Di Milia L, Natale V, Randler C. Circadian typology: a comprehensive review Chronobiol Int 2012; 29: 1153-75.], and related endophenotypes of neuropsy-chiatric importance, in healthy humans.

CONCLUSION

The PER3 VNTR polymorphism was not associated with either diurnal preference or daytime somnolence in a sample from the Colombian population. No significant differences in mean scores for those scales were found between PER3 VNTR genotypes. In addition, there were no differences in allelic or genotypic frequencies between chronotype categories. This is consistent with several negative findings in other populations, indicating that the proposed influence of this polymorphism in diurnal preference needs further clarification. This is one of the first reports of molecular genetics of human circadian phenotypes in a Spanish-speaking population and in subjects living in the equatorial region.

CONFLICT OF INTEREST

The authors confirm that this article’s content has no conflicts of interest.

ACKNOWLEDGEMENTS

This study was supported by grants from Colciencias (Contract # 765-2011), Universidad Antonio Nariño (VCTI-UAN) and Universidad de Ciencias Aplicadas y Ambientales (UDCA). The authors thank all those who assisted with recruitment of subjects.

REFERENCES

[1] Adan A, Archer SN, Hidalgo MP, Di Milia L, Natale V, Randler C. Circadian typology: a comprehensive review Chronobiol Int 2012; 29: 1153-75.
[2] Archer SN, Robilliard DL, Skene DJ, et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference Sleep 2003; 26: 413-5.
[3] Barclay NL, Eley TC, Mill J, et al. Sleep quality and diurnal preference in a sample of young adults: associations with 5HTTLPR.ER3.and CLOCK 3111. Am J Med Genet B Neuropsychiatr Genet 2011; 156B: 681-90.
[4] Dijk DJ, Archer SN. PERIOD3. circadian phenot pes.and sleep homeostasis. Sleep Med Rev 2010; 14: 151-60.
[5] Ebisawa T, Uchiyama M, Kajimura N, et al. Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome EMBO Rep 2001; 2: 342-6.
[6] Pereira DS, Tufik S, Louzada FM, et al. Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it? Sleep 2005; 28: 29-32.
[7] Nievergelt CM, Kripke DF, Barrett TB, et al. Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 234-41.
[8] Forero DA, Arboleda G, Yunis JJ, Pardo R, Arboleda H. Association study of polymorphisms in LRP1. tau and 5-HTT genes and Alzheimer's disease in a sample of Colombian patients J Neural Transm 2006; 113: 1253-62.
[9] Caci H, Adan A, Bohle P, Natale V, Pornpitakpan C, Tilley A. Transcultural properties of the composite scale of morningness: the relevance of the "morning affect" factor Chronobiol Int 2005; 22: 523-40.
[10] Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale Sleep 1991; 14: 540-.
[11] Smith CS, Folkard S, Schmieder RA, et al. Investigation of morning–evening orientation in six countries using the preferences scale Pers Individ Dif 2002; 32: 949-68.
[12] Thun E, Bjorvatn B, Osland T, et al. An actigraphic validation study of seven morningness-eveningness inventories Eur Psychol 2012; 17: 222-30.
[13] Adan A, Caci H, Prat G. Reliability of the Spanish version of the Composite Scale of Morningness Eur Psychiatry 2005; 20: 503-9.
[14] Choub A, Mancuso M, Coppede F, et al. Clock T3111C and Per2 C111G SNPs do not influence circadian rhythmicity in healthy Italian population Neurol Sci 2011; 32: 89-93.
[15] Kripke DF, Shadan FF, Dawson A, et al. Genotyping sleep disorders patients Psychiatry Investig 2010; 7: 36-42.
[16] Lazar AS, Slak A, Lo JC, et al. Sleep. diurnal prefernce.health., and psychological well-being a prospective single allelic-variation study Chronobiol Int 2012; 29: 131-46.
[17] Chica-Urzola HL, Escobar-Cordoba F, Eslava-Schmalbach J. [Validating the Epworth sleepiness scale] Rev Salud Publica (Bogota) 2007; 9: 558-67.
[18] Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies Bioinformatics 2006; 22: 1928-9.
[19] Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses Am J Hum Genet 2007; 81: 559-75.
[20] Osland TM, Bjorvatn BR, Steen VM, Pallesen S. Association study of a variable-number tandem repeat polymorphism in the clock gene PERIOD3 and chronotype in Norwegian university students Chronobiol Int 2011; 28: 764-0.
Track Your Manuscript:


Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents




Webmaster Contact: info@benthamopen.net
Copyright © 2020 Bentham Open